Lyophilization of nucleic acid nanoparticles

The objective of the thesis was the lyophilization of cationic
polymer-based pDNA or siRNA nanoparticles (i.e. polyplexes) with a
special focus on the development of long-term stable formulations,
the investigation of stabilization mechanisms especially during
freezing, and the advanced monitoring of the lyophilization
process. It was shown that an up-scaled preparation method in
combination with subsequent lyophilization is a promising approach
to reproducibly achieve long-term stable pDNA or siRNA polyplexes
maintaining particle size and biological activity at
pharmaceutically defined high quality. The results demonstrated
that formulation development, highly dependent on the used type of
polymer or nucleic acid, and process development, with a strong
focus on the freezing, in combination with appropriate process
monitoring needs always to be performed hand in hand. All in all,
this thesis makes an essential contribution in order to move closer
from a promising biotechnological approach towards clinic-friendly
drugs.